The most common treatment of Parkinson's Disease (PD) or other movement related disorders, who are not responsive to pharmacological intervention, is to stimulate the brain with small electrodes implanted into a region of the brain called the basal ganglia. The nuclei of the basal ganglia are found relatively deep within the brain. Accordingly, the treatment is often referred to as deep brain stimulation or DBS. It is now well established that high-frequency stimulation (˜150 Hz) from DBS electrodes provides relief to patients with movement disorders and estimates indicate that about 100,000 patients already received these implants. Based on the success in the treatment of PD, the DBS technique is now under evaluation for a wide range of new treatment modalities.
Despite its success, DBS is not without side effects. For example, implanted electrodes limit the applicability of magnetic resonance imaging (MRI) to examination of a patient with implanted electrodes. (In particular, heating, induced by MRI-generated radio-frequency waves that interact with the conductive leads, generates induced currents that result in the loss of energy in the form of heat.)
Another important side effect results when stimulation from a DBS electrode causes inadvertent activation of those neurons that are not involved in coordination of movement. This occurs primarily through activation of passing axons—the thin, fibrous projections of nerve cells that establish communication among neurons. Axons from several different regions of the brain pass adjacently to the basal ganglia and are highly sensitive to the stimulus waveforms used in DBS. For example, activation of axons associated with facial nerves are thought to underlie the facial twitches observed in PD patients that have DBS implants.
Magnetic stimulation of neurons is an attractive alternative to conventional electric stimulation. To implement the magnetic stimulation, the flow of electric current through a coil is used to induce a magnetic field according to Faraday's Law. This magnetic field, in turn, induces an electric field that can activate neurons. One of the attractive elements of magnetic stimulation is that the magnetic field passes readily through non-ferrous materials including skin and bone. As such, the magnetic field is less affected by the inflammatory reactions that tend to occur around implanted stimulating devices. In addition, because establishing the flow of current through a coil requires a complete, closed electrical circuit, an implanted coil is much safer than a conventional DBS electrode for use in MRI systems as no current leakage occurs to the ambient (surrounding) medium. Unfortunately, until now the focus of research activities into magnetic stimulation was on large coils (several inches in diameter) that can only be used externally. Recently, Tischler et al. (“Mini-coil for magnetic stimulation in the behaving primate”, J. Neurosci. Methods, v. 194, pp. 242-251, 2011) showed that coil diameters as small as 25 mm should activate neurons; although considerably smaller, such coils are still too large for implantation. More recently, a study by Bonmassar et al. (Microscopic Magnetic Stimulation of Neural Tissue, Nat. Commun., Jun. 26 2012; 3:921 doi: 10.1038/ncomms1914) showed that coils diameters as small as 0.5 mm could activate neurons. Flow of current levels in excess of 1 A through such coils was estimated to generate field strengths of about 10 V/m, comparable to the known thresholds of neuronal activation.
Bonmassar et al. disclosed a micro-magnetic stimulator (U.S. 2009/0254146) that included a magnetic coil small enough to be implanted in the brain tissue. Specifically, the coil of Bonmassar is comparable in size to a DBS electrode and capable of modulating neural activity. Such coils (and the associated system) represent a potentially attractive alternative to conventional DBS electrodes because they are MRI compatible. As further demonstrated in the above-mentioned “Microscopic magnetic stimulation of neural tissue” study, coils small enough to be implanted can in fact activate retinal neurons in vitro.
However, the problem of undesired activation, with such microcoils, of passing axons (causing unwanted physical reactions in the patients carrying implants) is not solved. Accordingly, there remains an unfulfilled need in a micro-system enabling magnetic stimulation of neural tissue in the brain that does not affect passing axons. In addition, the abovementioned system utilizes pulsatile stimulation that requires excessively high levels of current to elicit such activity.